The present invention is related to a specialized spectroscopic technique. Spectroscopy refers to the branch of analysis used for identifying elements and compounds and elucidating atomic and molecular structure by measuring the radiant energy absorbed or emitted by a substance at characteristic wavelengths of the electromagnetic spectrum (including gamma ray, X ray, ultraviolet, visible light, infrared, microwave and radio-frequency radiation) in response to excitation by an external energy source. The instruments used are spectroscopes (for direct visual observation) or spectrographs (for recording spectra). Spectroscopic systems include a radiation source, detectors, devices for measuring wavelengths and intensities, and interpretation of measured quantities to identify chemical identifications or give clues to the structure of atoms or molecules. Various specialized spectroscopy techniques include Raman spectroscopy, nuclear magnetic resonance (NMR), nuclear quadrupole resonance, dynamic reflectance spectroscopy, microwave and gamma ray spectroscopy, and electron spin resonance (ESR) spectroscopy or its synonym, electron paramagnetic resonance (EPR) spectroscopy.
Electron Paramagnetic Resonance is a spectroscopic analysis technique used to identify paramagnetic substances and investigate the nature of bonding within molecules by identifying unpaired electrons and their interaction with their intermediate surroundings. Unpaired electrons, because of their spin, behave like tiny magnets and can be lined up in an applied magnetic field. Energy applied by alternating microwave radiation is absorbed when its frequency coincides with that of the precession of the electron magnets in the sample. Precession refers to a change in the direction of the axis of a rotating body; the motion of a spinning body (e.g., as a top) in which it wobbles so that the axis of rotation sweeps out a cone. The obtained graph or spectrum of radiation absorbed as the field changes gives information valuable in chemistry, biology, and medicine.
Electron Paramagnetic Resonance (EPR) is a spectroscopic technique similar to Nuclear Magnetic Resonance (NMR). NMR is also known as magnetic resonance imaging (MRI). While NMR spectroscopy detects species containing magnetic nuclei such as H, 13C, 19F, EPR spectroscopy detects species with unpaired electrons. Examples of species with unpaired electrons are transition metal ions and free radicals. Magnetic Resonance Imaging (MRI) employs magnetic field gradients to generate anatomic images from objects abundant with water protons. The contrast agent induced spectral changes such as changes in spin-lattice relaxation (T1) and spin-spin relaxation (T2) times of protons provide functional information.
Recently available biologically compatible free radical contrast agents have made in vivo EPR imaging possible. The spectral changes in EPR are much more sensitive to the changes in the local environment than in MRI, making EPR imaging a potentially useful and complementary imaging technique to MRI.
In EPR, the object is irradiated with weak RF radiation continuously while sweeping the magnetic field relatively slowly, a technique known as CW EPR. Existing CW methodologies involve using a constant vector field gradient, a relatively slow sweep of magnetic field and the use of field modulation, a signal detection method known as phase-sensitive detection. This method takes typically at least 1-2 sec. for taking a single projection. However, most EPR imaging modalities use phase sensitive detection, which mandates several scans which are slow (seconds) making the image data acquisition times unacceptably long (e.g., 30 minutes) for in vivo applications.
Several EPR techniques are known. For example, U.S. Pat. No. 6,504,367, entitled “Electronic paramagnetic resonance imaging device using high amplitude modulator,” shows a conventional field sweep method using a field modulator along with phase sensitive detection. This reference does not teach or suggest the use of a direct detection scheme.
U.S. Pat. No. 6,472,874, entitled “EPR imaging device using microwave bridge translator,” describes a device which permits the acquisition of electron paramagnetic resonance images without employing additional hardware for generation of magnetic field gradients. It incorporates a module for translation of the bridge-circulator-resonator-detector assembly in order to locate the resonator at an optimal off-center position in the magnet and employs the inherent gradient in the magnetic field, permitting operation in either the continuous wave or pulsed mode. This reference shows a conventional field sweep method using a field modulator along with phase sensitive detection. This reference does not teach or suggest the use of a direct detection scheme.
U.S. Pat. No. 6,101,015, entitled “Variable-coupling quasioptical electron resonance apparatus,” describes a variable-coupling quasioptical electron paramagnetic resonance apparatus. This reference does not teach or suggest CW EPR, nor does it teach or suggest a direct detection modality, nor rotating magnetic fields.
U.S. Pat. No. 6,046,586, entitled “Crossed-loop resonator structure for spectroscopy,” describes a resonator structure including a first resonator having a first resonator loop formed by a hollow channel with conductive walls and a second resonator having a second resonator loop formed by a hollow channel with conductive walls. The detector circuit of the '586 patent detects the high frequency energy in the second resonator loop and supplies the detected signal for subsequent analysis. This reference teaches away from the use of CW in EPR.
Several other United Stated Public Health Service patents including: U.S. Pat. Nos. 5,387,867; 5,502,386; 5,828,216; 5,865,746; and 6,573,720 are also related to EPR modalities. However, none of these patent references disclose a CW EPR modality. All these references describe a conventional field sweep method using field modulation along with phase sensitive detection, and some are related to pulse mode as opposed to CW EPR imaging.
With regard to direction detection modalities, it is recognized that while direct detection may be known, it is not used with CW EPRI.
With regard to rotating magnetic field gradients, a reference by Ohno et al. (e.g. see Ohno et al., Electron Paramagnetic Resonance Imaging Using Magnetic-Field-Gradient Spinning, Journal of Magnetic Resonance 143:274-279 (2000)), and a reference by Deng et al. (e.g. see Fast EPR imaging at 300 MHz using spinning magnetic field gradients, Journal of Magnetic Resonance 168:220-227 (2004)) disclose sinusoidal/rotating magnetic field sweep in general, but not with direct detection. These references describe EPR modalities using low frequency modulation and relatively slow field scans, i.e., not with direct detection CW EPRI. Both of these references describe the use of field modulation and phase sensitive detection, which are the conventional ways of performing EPR and do not allow very fast field sweeps.
The use of a digital signal processor (DSP) is known in other signal processing areas. However, the use of a DSP in combination with (1) direct detection in the CW EPRI setup, allowing for faster scans; and (2) sinusoidal magnetic field sweep data acquisition under gradient magnetic fields, and rotating gradients is not yet known.
There is therefore a need for an EPR modality that does not suffer from the above shortcomings.